Following the revolutionaries' victory on 1 January 1959, he was appointed the director of medical services in Havana and later served as the national Minister of Health from 1960 to 1967, during which time he was responsible for the development of the country's health sector.[2] In January 1968, reportedly in the aftermath of a personal conflict with Fidel Castro over the running of the health sector,[2] he was appointed to serve as the Politburo's delegate in the province of Matanzas. He remained in Matanzas until mid-1971; his administration of the province's economy and health sector was successful, particularly in terms of crop outputs, public transport and reduced infant mortality.[2] Upon leaving Matanzas in 1971, he was appointed first secretary of the Cuban Communist Party in the province of Havana and was elected to the Politburo in December 1975.

Machado was elected by the National Assembly of People's Power as First Vice-President of the Council of State on 24 February 2008, at the same time as Raúl Castro's election as President;[4][5] he received 601 out of 609 votes.[4] Machado's election, at the age of 77, came as a surprise to some observers, who had been expecting someone younger to be chosen for the post.[6]